Chronic Ingestion of Lutein and Zeaxanthin in Primates

灵长类动物长期摄入叶黄素和玉米黄质

• 批准号: 6524977
• 负责人: FREDERICK KHACHIK
• 金额: $ 35.34万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6524977
• 关键词: Macaca mulatta; Raman spectrometry; aging; antioxidants; blood chemistry; carotenoids; cataract; dietary supplements; disease /disorder prevention /control; eye fundus photography; feces analysis; gel electrophoresis; high performance liquid chromatography; longitudinal animal study; macular degeneration; mass spectrometry; nutrient bioavailability; nutrient interaction; nutrition related tag; retinal pigment epithelium; retinoids; tocopherols; urinalysis; western blottings

An epidemiological study has concluded that high consumption of fruits and vegetables, rich specifically in two dietary carotenoids, lutein and zeaxanthin, reduces the risk of a degenerative eye disease called Age-related Macular Degeneration (AMD). High intake of carotenoid-rich fruits and vegetables results in the absorption of 25 dietary carotenoids which are converted to 9 metabolites in humans. Although all 34 carotenoids have been identified in human serum, milk, and tissues at varying concentrations, the major carotenoids found in the human retina, lens, and iris are lutein and zeaxanthin. In addition, two of the major oxidation products of lutein and zeaxanthin, 3'-oxolutein and 3'-epilutein, have also been shown to be present in retina and other ocular tissues at relatively low concentrations. One of the underlying hypothesis for the protective role of lutein and zeaxanthin has been based on the ability of these carotenoids to act as antioxidant and protect the human macula from photo-oxidation. The overall objective of his three-year proposal is to investigate the bioavailability, oxidative metabolism, retinal pigment density, and possible toxicity in primates supplemented with chronic and pharmaceutical doses of lutein, zeaxanthin, and their 1/1 combination. These studies will also evaluate possible interaction between lutein, zeaxanthin, and fat soluble vitamins such as vitamins A and E. In year one, chronic daily intake of lutein and zeaxanthin at a high dose of up to three hundred fold of the dietary levels, will be examined to establish safety or possible toxicity. In year two, 18 primates will be daily supplemented with lutein, zeaxanthin, and their 1/1 combination at a pharmaceutical dose of 0.5 mg/Kg/body weight to establish the optimum macular pigment density and correlate these values to plasma concentration of these carotenoids. In year three, 3 primates will be daily dosed with isotopically labeled zeaxanthin for a duration of six months. The study with labeled zeaxanthin allows the investigators to determine the possible metabolic conversion of this carotenoid to its oxidation products (metabolites) in serum and ocular tissues. The results from these studies will enable researchers to safely design and conduct clinical trials to investigate the efficacy of lutein and zeaxanthin supplementation in the prevention and treatment of AMD and cataract. Lutein/zeaxanthin supplements have widely used as a nutritional supplement un the U.S. since 1995, while safety and efficacy of these carotenoids has not yet been established.

一项流行病学研究得出的结论是，大量食用水果和蔬菜，特别是在两种饮食类胡萝卜素中富含叶黄素和玉米黄质，降低了称为年龄相关的黄斑变性（AMD）的退化性眼病的风险。 高摄入类胡萝卜素的水果和蔬菜的摄入量会导致25种饮食类胡萝卜素的吸收，这些类胡萝卜素被转化为人类的9个代谢产物。 尽管在人类血清，牛奶和组织中均以不同浓度的组织中鉴定出所有34种类胡萝卜素，但在人视网膜，镜头和虹膜中发现的主要类胡萝卜素是叶黄素和玉米蛋白。 此外，叶黄素和玉米黄质，3'-氧化素和3'-尿素蛋白的两种主要氧化产物也已显示出在视网膜和其他眼组织中存在于相对较低的浓度中。 叶黄素和玉米黄蛋白保护作用的基本假设之一是基于这些类胡萝卜素充当抗氧化剂并保护人黄斑免受光氧化的能力。 他三年提案的总体目的是研究补充了lutein，Zeaxanthin及其1/1组合的灵长类动物的生物利用度，氧化代谢，视网膜色素密度以及可能的毒性。 这些研究还将评估叶黄素，玉米黄质和脂溶性维生素（例如维生素A和E）之间的可能相互作用。在第一年，将慢性每日摄入叶黄素和玉米黄质摄入量高达三百倍的饮食水平，以确定以确定安全性或可能的毒性或可能的毒性。 在第二年，每天将有18个灵长类动物补充叶黄素，玉米黄蛋白，并以0.5 mg/kg/体重的药物剂量下的1/1组合，以建立最佳的黄斑色素密度并将这些值与这些类胡萝卜素的血浆浓度相关联。 在第三年级，每天将有3个灵长类动物的同位素标记为Zeaxanthin持续六个月。 用标记为Zeaxanthin的研究允许研究人员确定该类胡萝卜素对血清和眼组织中其氧化产物（代谢产物）的代谢转化。 这些研究的结果将使研究人员能够安全设计和进行临床试验，以研究叶黄素和Zeaxanthin补充剂在预防和治疗AMD和白内障中的疗效。自1995年以来，叶黄素/Zeaxanthin补充剂已被广泛用作美国的营养补充剂，而这些类胡萝卜素的安全性和功效尚未确定。